Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

When nanomaterials meet the biological world, the cellular interaction of nanoparticles is routinely assessed in in vitro systems. Establishing dose-response relationships requires that the dose of nanoparticles delivered to the cell is accurate and precise. Nanoparticles as such or coated with high molecular-weight compounds are rarely uniform and the influence of heterogeneity, including polydispersity both in size and mass density, on the delivered dose is never studied before. Furthermore, a probabilistic term describing particle adherence to cells is introduced and the importance is discussed. By tracing the movement of discrete particles via modeling, it is found that the influence of heterogeneity cannot be neglected when the average particle size promotes settling over diffusion. However, the influence of polydispersity on the delivered cellular dose is less critical for particulate systems whose mean size promotes diffusion. The influence of a non-instantaneous particle association to the cell is negligible for particles whose motion is dominated by settling, but it is relevant for small particles whose motion is governed by diffusion.